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Skeletal unloading and cephalic fluid shifts in microgravity may alter the bone microvascular flow and may be associated with the 1-2% bone loss per month during spaceflight. The purpose of this study was to determine if lower-body negative pressure (LBNP) can prevent mi-crogravity-induced alterations of tibial microvascular flow. Head-down tilt (HDT) simulates the cephalad fluid shift and microvascular flow responses that may occur in microgravity. We hypothesized that LBNP prevents HDT-induced increases in tibial microvascular flow. Tibial bone microvascular flow, oxygenation, and calf circumference were measured during 5 min sitting, 5 min supine, 5 min 15° HDT, and 10 min 15° HDT with 25 mmHg LBNP using photoplethysmog-raphy (PPG), near-infrared spectroscopy (NIRS), and strain-gauge plethysmography (SGP). Measurements were made simultaneously. Tibial microvascular flow increased by 36% with 5 min 15° HDT [2.2 ± 1.1 V; repeated-measures ANOVA (RMANOVA) P < 0.0001] from supine (1.4 ± 0.8 V). After 10 min of LBNP in the 15° HDT position, tibial microvascular flow returned to supine levels (1.1 ± 0.5 V; RMANOVA P < 0.001). Tibial oxygenation did not change significantly during sitting, supine, HDT, or HDT with LBNP. However, calf circumference decreased with 5 min 15° HDT (-0.7 ± 0.4 V; RMANOVA P < 0.0001) from supine (-0.5 ± 0.4 V). However, with LBNP calf circumference returned to supine levels (-0.4 ± 0.1 V; RMANOVA P = 0.002). These data establish that simulated microgravity increases tibial microvascular flow and LBNP prevents these increases. The results suggest that LBNP may provide a suitable countermeasure to normalize the bone microvascular flow during spaceflight. [ABSTRACT FROM AUTHOR]